Revising Entry Criteria Key to Maximizing Clinical Trial Participation

Revising Entry Criteria Key to Maximizing Clinical Trial Participation

Dr. Julia A. Beaver
Mary Jackson Scroggins
The Education Session “Strategies to Maximize Patient Participation in Clinical Trials,” to be held on June 4,* will look at how to improve efficiencies so that clinical trials run faster and will evaluate why some studies do not enroll patients effectively.

“Our hope for the session is to bring a renewed awareness to the issues and to discuss potential solutions,” said Session Chair Julia A. Beaver, MD, of the U.S. Food and Drug Administration (FDA).

“This is an important topic, one that’s relevant to all the stakeholders in the field—patients, academic practicing oncologists, and industry regulators. We’re all trying to improve clinical trial participation,” said Session Speaker Eric H. Rubin, MD, of Merck Research Laboratories.

Dr. Beaver will discuss updates from the ASCO and the Friends of Cancer Research Modernization of Eligibility Criteria project, “which, in collaboration with the FDA, is working toward recommendations for a more rational approach to determining inclusion and exclusion criteria for clinical trials,” she said. “We’ve been actively engaged in this issue at the FDA, and we are eager to continue the discussion so we can move toward implementable solutions for rationalizing the approach to eligibility criteria.”

Mary Jackson Scroggins, MA, a 20-year ovarian cancer survivor and patient advocate, will focus on improving access to and participation in clinical trials across populations, with particular interest in medically underserved and underrepresented populations.

Modernizing approaches to clinical trials to streamline eligibility criteria may help overcome some of the dilemmas clinicians face, Dr. Rubin said. “In the modern age of newer medications, some of the holdover criteria really do not apply, and we need to evaluate how to make entry criteria less restrictive,” Dr. Rubin said.

Dr. Beaver said “overly restrictive eligibility criteria” can also limit patient enrollment, reduce access to investigational agents for trial enrollees, and may impact the interpretability of the trial results in a more representative patient population.

Understanding Causes of Low Clinical Trial Enrollment

With numerous reasons for low clinical trial accrual rates—including those that stem from barriers at patient, physician, institutional, and protocol levels—other issues include how quickly the field of cancer care treatment is moving overall.

“Low rates of clinical trial participation continue to impair the clinical trial system/enterprise, decreasing the speed and likelihood of trial progress and, thus, ultimate patient benefit, wasting precious human and funding resources, and compromising confidence in the system,” Ms. Scroggins said. “Low trial enrollment is a recurring topic or theme at most trial-related meetings; progress does not match or reflect the frequency of coverage.”

Patients who fear clinical trials “will delay initiation of standard cancer drugs or require additional morbid testing and procedures,” Dr. Beaver said. “In addition, availability of clinical trials at a given institution varies, and there may be a lack of knowledge regarding potential clinical trials for patient referral.”

Dr. Rubin recalled a clinical study a few years ago that was evaluating a novel treatment for colon cancer.

“There were emerging data on the EGFR inhibitors, and it was clear they were ineffective in tumors with KRAS mutations,” he said.

It would have been unethical to continue enrolling patients who may have been randomized to an ineffective arm—another reason to speed patient accrual, he said. Faster patient accrual will lead to quicker analysis of data, which may help evolve the standard of care in specific cancers in a more timely manner, he said.

Dispelling myths around clinical trial participation—from the thought that the Tuskegee syphilis study is the reason for low enrollment of specific populations to the belief that some trial participants will receive less than standard of care—is imperative, Ms. Scroggins said. Modernizing the eligibility requirements on aspects such as exclusion criteria related to comorbidities “can have a profound effect on enrolling specific populations and result in trial populations more reflective of the general population and/or of the disease burden across populations,” she said.

The FDA has worked diligently with industry and patient advocate groups to revisit the criteria used for patient eligibility with “the ultimate goal of opening new opportunities for patient participation in trials and to enhance the generalizability of what we could learn from this,” Dr. Beaver said, bearing in mind that any adjustments cannot be at the cost of patient safety.

Master Protocols

Dr. Rubin believes newer approaches gaining traction and prominence include “master protocols” that can potentially involve multiple companies.

In these approaches, the whole clinical trial process benefits from efficiencies because instead of each sponsor having its own two-armed randomized study with similar (if not identical) control arms, “we can merge all the data into one master study, and that becomes much more efficient from an overall system perspective,” Dr. Rubin said. There is a current ongoing lung cancer master protocol that is using this approach, but Dr. Rubin acknowledged that some issues emerged as the standard of care changed “right as the protocol and recruitment were ramping up.”

Take-Home Messages

Dr. Beaver hopes the take-home messaging is twofold for attendees: first, to “refocus stakeholders to the knowledge and importance of [clinical trial enrollment], and second, to realize that to improve the current state of affairs, a collaborative multi-stakeholder effort will be required,”
she said.

From a patient and patient advocate perspective, Dr. Rubin said master protocols are attractive because patient selection will be more robust and individualized based on the genetic makeup of the tumor.

“In this age of research on personalized medicine and health care, representative trial participation across populations is a must,” Ms. Scroggins said, otherwise underrepresented populations are unlikely to benefit from the research.

“Matching a specific type of mutation or characteristic of the patient’s tumor to a subset within a master protocol that is evaluating potential therapies is an attractive potential for patients,” Dr. Rubin said.

“There is an abundance of new information in our session,” he continued. “Whether you’re a patient, an academician, or an industry [member] or a regulator, how to construct trials and maximize patient recruitment is relevant to everybody.”•

—Michelle Dalton, ELS

*Program information updated as of May 15. For session time and location information, please refer to the ASCO iPlanner on the Attendee Resource Center.